The present invention relates to a gelatin hard capsule enhancing the strength of film. More particularly, this invention relates to a gelatine hard capsule having enhanced strength of film and equal film distribution prepared by the steps comprising i) adding polyethylene glycol (PEG) and acetyl glycerine fatty acid ester to gelatin aqueous solution; and ii) forming and drying the gelatin mixture.
In particular, this invention concerns gelatin hard capsule having minimum cracking or chipping in low moisture condition prepared by the steps comprising i) selecting PEG among PEGs having average M.W. 200˜20,000; ii) preparing proper PEG mixture using selected PEGs; iii) adding said PEG mixture with acetyl glycerine fatty acid ester as plasticizer to gelatin aqueous solution; and iv) forming and drying the gelatine mixture to obtain gelatin hard capsule.
Gelatin reversibly changes its phase from sol into gel according to the change of temperature. The water content of gelatin film is 13˜16% and gelatine capsules are widely used in the field of pharmaceutical or food stuff preparation. However, conventional hard gelatin capsules have a problem in that the capsule film loses flexibility and suffers cracking or chipping if the capsules are packed with a hygroscopic drug such as a powder or granular material since the moisture contained in the capsule film is adsorbed by the drug.
To solve above problems, addition of PEG to gelatin film composition has been suggested.
Japanese laying open patent publication No. 3-80930 ‘Composition of gelatin film’ disclosed the gelatin film composition comprising polyethylene glycol of average M.W. 200˜20,000. Among them, at least one PEG selected from the group consisting of 200, 300, 400, 600, 1000, 1500, 1540, 4000, 6000 and 20000 has been disclosed. However, there is no description which M.W. of PEG is selectively proper for protecting the decline of water content in gelatine capsule.
In Japanese Pat. No. 3,320,802, gelatine hard capsule film composition comprising 1˜10 wt % of polyvinylacetyldiethylaminoacetate and 1˜10 wt % of PEG as to gelatin has been disclosed. This gelatin film composition can be used for protecting the decline of water content of gelatin film when hygroscopic drug is contained. Further, this gelatin film composition affords the minimum cracking or chipping, which prevents the leakage of drug.
In Japanese Pharmacopoeia, 5 kinds of PEGs, according to the size of M.W., 400, 1500, 4000, 6000, 20000 are described. In the Japanese specification of drug additive, 5 kinds of PEGs 200, 300, 600, 1000, 1540 are described. However, in Japanese Pat. No. 3,320,802, it has not been specifically disclosed which PEG among them is desirously used, except that PEG 4000 is proper in this disclosure.
On the other hand, Japanese Pat. No. 3,594,111 discloses a preparation method for hard capsule according to the dipping method by addition of PEG 1540 to gelatin aqueous solution. In this disclosure, the method comprises i) adding 10˜50 wt % of PEG 1540 as to gelatin content in gelatin aqueous solution; and ii) forming gelatin hard capsule according to dipping method. The PEG added to gelatin is only PEG 1540 in this disclosure.
Gelatin hard capsule has been manufactured using the characteristics of gelatin having setting point at 25˜28° C. To obtain a flat film minimizing the cracking or chipping with equal film distribution, it is required that the setting point of PEG added to gelatin solution shall be same or similar to that of gelatin, which enables the flow of gelatin mixed solution to be constant at the mold pin after dipping.
Because 10 kinds of PEGs described in Japanese Pharmacopoeia and Japanese specification of drug additive have different physical properties such as setting point and viscosity, the selection of proper PEG has been required to achieve the gelatin hard capsule having equal film distribution and minimum cracking or chipping.
However, it has not been disclosed yet which grade of PEG is compatible to gelatin base to accomplish the enhancement of film strength and protection of decline of water content when hygroscopic material is inserted.
The inventors have developed a gelatin hard capsule by adding proper PEG mixture to gelatin, which enhances the film strength when hygroscopic material is inserted. Further, this gelatin hard capsule has equal film distribution with minimum cracking or chipping when hygroscopic material is inserted.